Bio‐Hybrid Cell‐Based Actuators for Microsystems

Abstract

As we move towards the miniaturization of devices to perform tasks at the nano and microscale, it has become increasingly important to develop new methods for actuation, sensing, and control. Over the past decade, bio-hybrid methods have been investigated as a promising new approach to overcome the challenges of scaling down robotic and other functional devices. These methods integrate biological cells with artificial components and therefore, can take advantage of the intrinsic actuation and sensing functionalities of biological cells. Here, the recent advancements in bio-hybrid actuation are reviewed, and the challenges associated with the design, fabrication, and control of bio-hybrid microsystems are discussed. As a case study, focus is put on the development of bacteria-driven microswimmers, which has been investigated as a targeted drug delivery carrier. Finally, a future outlook for the development of these systems is provided. The continued integration of biological and artificial components is envisioned to enable the performance of tasks at a smaller and smaller scale in the future, leading to the parallel and distributed operation of functional systems at the microscale.

Device and programming abstractions for spatiotemporal control of active micro-particle swarms

“…Directing swarm behaviours within microfluidic chips is necessary to harness active systems for various biomedical, environmental, or synthesis applications. 1,15,18,26 Furthermore such systems can be used for STEM education or research at the intersection of computer and life-sciences. 52,53 Compared to previous interactive biology setups, 30,31,38,39 this system adds a programmable layer to the BPU with feedback controls, easing application development.…”

“…For other swarm systems, the stimuli set will vary to achieve these commands. 1,18,22,25,35,36 However, the commands themselves are general methods for manipulating matter, and thus are broadly applicable. Finally, system-level commands require the system to be able to monitor its state (i.e.…”

“…[1][2][3][4][5][6][7][8][9] Controlled swarm motion may be employed to generate flows in lab-onchip devices in conjunction with digital microfluidics, [1][2][3][4][5][10][11][12] on-chip computation as previously explored with droplet logic and neural computation, 7,13 cargo delivery, 6,[14][15][16] and for selfassembly of nano-and microdevices. 8,10,15,[17][18][19][20] Algorithms for efficient control and programming of such swarms have been extensively studied via theory 20,21 and experiment in both synthetic 22 and natural systems, from motor proteins and filaments 23,24 to single-celled organisms 2,8,25,26 to insects 27 to macroscopic robots. 20,21,28 For microbiological swarms, "interactive biology" setups have enabled both professionals and non-experts to interact and experiment with swarm agents in real-time for research and edutainment purposes, e.g., through biology cloud experimentation laboratories, 29,…”

Fabrication of nanocomposites and hybrid materials using microbial biotemplates

“…These respond to an environmental stimulus; this property can be applied as a mean to steer the microbe-driven devices, such as microswimmers. Thus, a single bacterium can serve as microswimmer and can find potential applications in medicine and bioengineering, such as targeted drug, gene, and imaging agent delivery, biosensing, and cell transportation [57]. Besides, functional microparticles can be attached to a single bacterium; such biohybrid microswimmers can be used for targeted drug delivery [58].…”

Stimulus-active polymer actuators for next-generation microfluidic devices

“…Although these systems come with challenges related to increasing lifetime and issues with packaging, they open up promising new pathways, for instance, co-culturing of muscle cells with neuronal cells to recreate neuromuscular junctions for use in microsystems. Carlsen et al [22] gave in a thorough review of the latest advances in the field of biohybrid cell-based actuators, including an innovative approach to realizing 3D selfassembled engineered PDMS substrates which are used as enabling matrices to align muscle cells [23], the use of confined bacteria as building blocks to generate fluid flow [24], and the discovery that cardiomyocyte cells are capable of (1) sensing substrate deformations via a mechanosensitive feedback mechanism and (2) dynamically reorganizing themselves [25]. Though bionic concepts can be rated as an exciting pathway for future research, robustness and reliability of the components presented by now is by far not sufficient for real application in microfluidics.…”